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Parkinsons and Epilepsy Flashcards

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1
Q

Parkinsons disease

A

Neurodegenerative disorder consisting of loss of dopaminergic neurones in the substantia nigra leading to degeneration of projections

1% incidence, increases with age and male gender

PC - bradykinesia, resting tremor, rigidity and postural instability. Autonomic symptoms of postural hypotension, urinary incontinence, constipation and erectile dysfunction

1st symptoms = anosmia, depression/anxiety, sleep disturbance,

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2
Q

Parkinsonism

A

Clinical signs and symptoms of PD may be caused by MSA, huxngtingtons or small vessel ischemia

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3
Q

Sites for medication to act in PD

A

Levodopa - replaces missing dopamine
Monoamine oxidase inhibitors - prevent dopamine breakdown
Dopamine agonists - mimic dopamine actions by binding to the post synaptic receptor
COMT inhibitors - prevent breakdown at synaptic cleft

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4
Q

L-dopa (madopar = co-careldopa) MOA

A

Precursor for dopamine given with decarboxylase inhibitor to prevent its breakdown peripherally. Without this only 5% would reach the brain and SE of dopamine peripherally would be N/V, arrhythmias and postural hypotension

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5
Q

Short term SE L-dopa

A

N/V, reduced appetite
Somnolence, insomnia and vivid dreams
Postural hypotension - vasodilation of cardiac vessels

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6
Q

Long term SE L-dopa

A

Motor compilations 50% pt @ 5 years = wearing off of dose requiring increase strength preparations, on off switching and freezing

Dyskinesia = continual writhing, rocking or fighting movements. Dose related. To reduced effects take with meals, small frequent doses and use adjunct medications

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7
Q

CI L-dopa

A

Heart failure, arrhythmias. Closed angle glaucoma

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8
Q

Interactions of L-dopa

A

MAOI’s increased risk of hypertensive crisis
Antihypertensives = increased effect

Warn pt about driving or operating heavy machinery due to drowsiness or dyskinesia

Don’t abruptly stop taking medication = rhabdomyolysis or neuroleptic malignant syndrome

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9
Q

Dopamine agonists (Ropinerole or rotigotine)

A

Mimics effect of dopamine by binding to post synaptic receptors in striatum. Not used in elderly due to reduced efficacy compared to L-dopa and can have increased psychotic effects

1st line in patients <70y/o newly diagnosed

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10
Q

SE of dopamine agonists

A

Somnolence, confusion and hallucinations
N/V and reduced appetite

Impulse control disorders 15% hyper sexuality, gambling, shopping sprees

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11
Q

CI drugs in PD

A

Dopamine antagonists = haloperidol

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12
Q

Mono-amine oxidase B inhibitors (Selegline/rasagiline)

A

Irreversibly inhibit MOAB the specific enzyme for dopamine breakdown after reuptake from the synaptic cleft

Used as an adjunct to L-dopa

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13
Q

SE of MAOBi

A

N/V, confusion and insomnia, postural hypotension

Increase risk of serotonin syndrome

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14
Q

Catechol-O-methyl-tranferase inhibitors (Entacapone)

A

Inhibit COMT, this enzyme is responsible for breakdown of dopamine at the synaptic cleft. Prolongs its action at the post synaptic receptor

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15
Q

SE COMT

A

Increased risk of dyskinesias, diarrhoea, reddish brown urine. Tolcapone is more effective but increased risk of hepatotoxcity

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16
Q

Amantidine

A

Acts as a minor antimuscarinic, stimulating dopamine release and inhibiting its reuptake. Can reduced dyskinesia

SE = ankle oedema, postural hypotension and confusion

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17
Q

Treatment of PD 50-60y/o and >70y/o

A

<70y/o and new diagnosis = MAOI and dopamine agonists. L-dopa sparing strategy

> 70y/o / comorbidities = L-dopa +/- MAOBi or COMT

If severe dyskinesia reduce dose of L-dopa and start amantadine

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18
Q

Mx PD complications

A

Anxiety/ insomnia = CBT, SSRI’s, Zopiclone
Constipation = hydration, laxatives
Nocturne and incontinence = catheter?

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19
Q

Drug induced Parkinsons

A

Dopamine antagonists = haloperidol, metacloprimide

Lithium, sodium valproate, fluoxetine

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20
Q

Hypertensive emergency vs Hypertensive crisis

A

Emergency = High blood pressure and acute impairment of 1+ organ systems

Hypertensive crisis = BP >180 no evidence of organ damage

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21
Q

PC hypertensive emergency and Mx

A

Retinal haemorrhages and papilloedema
increased ICP = headache, vomiting, low GCS,
Acute renal failure = haemturia and proteinuria

Mx IV sodium nitroprusside

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22
Q

Complications of HTN emergency

A

Hypertensive encephalopathy, CVA, inter cranial haemorrhage. MI, LV dysfunction, AKI

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23
Q

Causes of HTN emergency

A

Pregnancy, cocaine, Phaechromocytoma, head trauma, dopamine agonist, MAOI, renal artery stenosis

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24
Q

Epilepsy and seizures definition

A 
Epilepsy = predisposition to having seizures
Seizure = A clinical symptom caused by abnormal electrical discharge in the brain
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25
Generalised seizures
Loss of consciousness, discharge over the entire cortex Include absence seizures, tonic-clonic, myoclonic Mx = sodium valproate
26
Partial seizures
Focal onset, consciousness maintained Simple and complex - then can turn into generalised seizures Often demonstrate automatism seen due to activity at temporal lobe = smacking of lips, chewing, clapping of hands. Can include olfactory hallucinations Mx = carbamazepine
27
Causes of epilepsy
Congenital - cerbral palsy, idiopathic, head injury, post stroke or meningitis
28
Guide to epilepsy Mx
Antiepileptics prescribed after 2x distinct episodes Monotherapy unless treatment resistant Never withdraw abruptly Seizure of any type inform DVLA
29
Causes of Seizures
``` Vascular = stroke, SAH Infections = sepsis, meningitis, encephalitis Trauma = head injury Metabolic = hypoglycemia, hypo/hyperthermia, electrolyte abnormalities, hypoxia Inflammatory = amyloidois, alzheimers Neoplastic = SOL Doctors = drugs cocaine, MDMA, alcohol, ```
30
Sodium Valproate MOA
Valproate acts on Na+, Ca2+ channels and GABAa receptors. It inhibits GABA transaminase therefore increasing GABA level leading to neuronal inhibiton
31
Sodium Valproate uses
1st line for idiopathic generalised epilepsy, myoclonic and absent seizures
32
SE sodium valproate
wt gain, N/V, impaired glucose tolerance, tremor Highly teratogenic don't use in pregnancy Can = acute liver failure monitor LFT's 6 monthly thrombocytopenia pancreatitis Hyperammonemia = risk of encephalopathy
33
Interactions of sodium valproate
CYP450 inhibitor = increased effect of warfarin, theophylline, lamotrigine
34
Ethosuximide
Blocks specific Ca2+ channels that are active in generalised seizures. Used 1st line for children with absent seizures
35
Drugs to avoid in absent/myoclonic seziures
Carbamazepine, phenytoin, gabapentin and pregabalin
36
SE of ethosuximide
GI upset, eosinophilia, potentiation of tonic clonic seizures
37
Carbamazepine MOA
Blocks voltage gated Na+ channels reducing membrane excitability preventing the propagation of action potentials. Opens K+ channels promoting GABA release.
38
Carbamazepine 1st line
All partial seizures and trigeminal neuralgia
39
SE Carbamazepine
Skin reaction and rash, can = SJS Dose related = ataxia, diplopia and vertigo/dizziness Osteomalacia and folate defence leukopenia and thrombocytopenia
40
Interactions of carbamazepine
Enzyme inducer - can induce its own metabolise soma need to gradually be titrated up during initial weeks of Mx
41
CYP450 inhibitors
Sodium valproate, isoniazid, macrolides amiodarone, SSRI, quinolones, PPI, grapefruit
42
CYP450 inducers
Carbamazepine, phenytoin, theophylline, rifampicin, ST johns wart
43
Phenytoin MOA
Blocks propagation of action potentials by preferentially blocking excitation of neurones that are repeatedly firing. Discourages spread not initiation. Acts on Na+ channels Enzyme inducer so dose may need to be titrated up, reduces effective dose of other drugs
44
Uses of phenytoin
Status epileptics and myotonic dystrophy
45
SE of phenytoin
Narrow therapeutic window so can = toxicity gingival hypertrophy due to inhibition of collagen catabolism. Acne, hirsutism, insomnia, peripheral neuropathy, tremor, dyskinesia Macrocytic anaemia due to increasing folate metabolism, osteomalacia due to increased vit d metabolism
46
Screening of chinese/thai on phenytonin
HLAB-1502 gene which gives a increased incidence of SJS
47
Acute phenytoin toxicity PC
Severe cerebellar signs - ataxia, diplopia, dysmetria, nystagmus, dysdokinesia Drowsiness, needs cardiac and BP monitoring IV phenytoin may - hypotension, arrhythmias, cardiac and rep depression
48
CI to phenytonin
Teratogenic, HLAB-1502 +ve, heart block
49
Lamotrigine MOA
Stabilises pre-synaptic neuronal membranes by blocking voltage gated Na+ and Ca2+, reducing the release of glutamate and excitatory neurotransmitter Alternative for generalised and partial epilepsy safest in pregnancy!
50
SE lamotrigine
Increased incidence of SJS and TEN, 10% of people experience a rash (start low and increase dose gradually) GI disturbance Stop if signs of rash, monitor LFT's and FBC
51
Levertircetam
Future drug of choice. Inhibits synaptic vesicle protein 2A reducing vesicle recycling and inhibiting presynaptic Ca2+ channels Well tolerated, few drug interactions. Renally excreted
52
SE Levertircetam
labile mood, somnolence, behavioural disturbance and psychosis
53
COCP and antiepileptics
Reduced efficacy of COCP = carbamazepine, phenytoin COCP reduces the efficacy of lamotrigine Use increased strength COCP 50micrograms or mirena coil as alternative
54
Benzodiazepines (diazepam/midalozam) MOA
Agonists to the benzodiazepam receptor on GABA receptor complex. High affinity for GABA receptor bind causing Cl- channels to open hyperpolarising the membrane preventing further excitation.
55
Uses of benzodiazepines
Status epilepticus, alcohol withdrawal - seizures prophylaxis, sedation, short terms anxiety relief
56
SE benzodiazepines
Confusion, amenesia, hypotension Can = respiratory depression If long term lead to dependence If overdose = IV flumazenil
57
Status epilepticus
5+ minutes of seizure activity or several recurrent seizures in 30mins
58
Mx status epilepticus
ABCDE - protect airway. Check glucose = hypoglycaemia is a common cause of seizures IV lorazepam 0.07mg/kg stat Alternatives in community = PR diazepam or buccal midolozam If no improvement in 20mins IV phenytoin 15mg/kg, monitor BP, HR, ECG. Inform ITU
59
Sudden unexpected death epilepsy risk factors
Young age, poor control/compliance, generalised tonic/clonic, unwitnessed seizures
60
Pregnancy and anti epileptics
High dose folic acid 5mg for all. Lamotrigine is the safest in pregnancy. Aim to give mono therapy at lowest possible dose. Don't prescribe valproate
61
Driving and seizures
With any seizure not due to a reversible cause i.e. alcohol, drugs or fever cease driving and inform DVLA immediately 1st unprovoked seizure = 6 month ban Established epilepsy = 1 year seizure free
62
Wernickes encephalopathy
Triad of ataxia, confusion and opthalmeplegia - nystagmus. Due to thiamine deficiency seen commonly in alcoholics
63
Korsakoff psychosis
Anterograde and retrograde amnesia due to maxillary body infarction due to chronic thiamine deficiency. LTM is maintained. Occasionally confabulation
64
Delirium tremens
Alcohol is an inhibitory of the CNS, rapid withdraw leads to reduced GABA = mass overexcitation. Worse 2-3 days post withdrawal
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Mx acute alcohol withdrawal
ABCDE + correct hypoglycaemia 2 x 500mg thiamine IV TDS IV chlordiazepoxide
66
PC Delirium tremens
Confusion, agitation, visual and auditory hallucinations, sweating, tachycardia, hyperthermia, tremors, N/V Can lead to generalised tonic-clonic seizures. O/E = high HR and BP, pyrexial, tremor, nystagmus, reduced GCS
67
Antiepileptic hypersensitivity
Rare but fatal complication linked to carbamazepine, lamotrigine and phenytoin. Symptoms 1-8 wks post exposure. PC = fever, rash, lymphadenopathy, liver dysfunction, renal failure

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